On Location 2015 ASH Annual Meeting
of events; the presentation at the ASH
annual meeting included results from the
second interim analysis.
At the time of data presentation, 346
events had occurred over a median followup of 39 months: 197 in the RVD arm and
149 in the AHCT arm. All patients had
discontinued treatment, with 66 percent
having completed planned therapy; 16
percent experienced disease progression,
and 10 percent experienced adverse events
(AEs) that led to discontinuation.
AHCT was found to improve progression-free survival (PFS; the study’s primary
endpoint), with a three-year PFS rate of
61 percent in the transplant arm versus 48
percent in the RVD arm (hazard ratio [HR]
= 1.5; 95% CI 1.2-1.9; p<0.0002).
B:8.5”
Notably, the PFS benefit was observed
T:8.25”
and uniform across the following subS:7”
groups in the AHCT
group: age (≤ or >60
years), sex, Ig isotype (IgG or others), ISS
The detection of antibody formation is dependent on the sensitivity and
specificity of the assay. Additionally, the observed incidence of antibody
(including neutralizing antibody) positivity in an assay may be influenced by
several factors including assay methodology, sample handling, timing of sample
collection, concomitant medications, and underlying disease. For these reasons,
comparison of the incidence of antibodies to Kogenate FS with the incidence of
antibodies to other products may be misleading.
6.2 Postmarketing Experience
Because adverse reactions are reported voluntarily from a population of uncertain
size, it is not always possible to reliably estimate their frequency or establish a
causal relationship to drug exposure. The following adverse reaction has been
identified during post approval use of Kogenate FS:
Sensory System – Dysgeusia
Immunogenicity – Postmarketing Registries
Data from the Research of Determinants of Inhibitor Development (RODIN)
study7, French National Registry (FranceCoag)8 and United Kingdom
Haemophilia Centre Doctors’ Organisation (UKHCDO)9 registry reported an
inhibitor development rate in PUPs for Kogenate FS of 38%, 50% and 35%,
respectively, which is comparable to previously-reported inhibitor rates10 for
FVIII products. These registry studies show a trend towards an increased risk
of inhibitor development in PUPs, as compared to the reference rFVIII product.
A survey of Canadian hemophilia centers11 (2005 to 2012) and available data
from the European Haemophilia Safety Surveillance (EUHASS) 12 registry from
2009 to 2013, reported an inhibitor development rate in PUPs for Kogenate FS of
42% and 31%, respectively, with no sta tistically significant differences observed
across FVIII products.
8
USE IN SPECIFIC POPULATIONS
8.1 Pregnancy
Pregnancy Category C.
Animal reproduction studies have not been conducted with Kogenate FS. It is
also not known whether Kogenate FS can cause fetal harm when administered to
a pregnant woman or affect reproductive capacity. Kogenate FS should be given
to a pregnant woman only if clearly needed.
8.5 Geriatric Use
Clinical studies with Kogenate FS did not include patients aged 65 and over. Dose
selection for an elderly patient should be individualized.
Bayer HealthCare LLC
Whippany, NJ 07981 USA
U.S. License No. 8
(License Holder: Bayer Corporation)
http://www.kogenatefs.com/
6709903BS
REFERENCE
Attal M, Lauwers-Cances V, Hulin C, et al. Autologous
transplantation for multiple myeloma in the era of new drugs:
a phase III study of the Intergroupe Francophone Du Myelome
(IFM/DFCI 2009 Trial). Abstract #391. Presented at the 2015 ASH
Annual Meeting, December 6, 2015; Orlando, Florida.
B:11.125”
8.4 Pediatric Use
Safety and efficacy studies have been performed in previously untreated and
minimally treated pediatric patients. Children, in comparison to adults, present
higher factor VIII clearance values and, thus, lower half-life and recovery of
factor VIII. This may be due to differences in body composition.13 Account for
this difference in clearance when dosing or following factor VIII levels in the
pediatric population [see Clinical Pharmacology (12.3)].
Routine prophylactic treatment in children ages 0–2.5 years with no pre-existing
joint damage has been shown to reduce spontaneous joint bleeding and the risk
of joint damage. This data can be extrapolated to ages >2.5–16 years for children
who have no existing joint damage [see Clinical Studies (14)].
17 PATIENT COUNSELING INFORMATION
• Advise the patient to read the FDA-approved patient labeling (Patient
Information and Instructions for Use).
• Advise patients to report any adverse reactions or problems following
Kogenate FS administration to their physician or healthcare provider.
• Allergic-type hypersensitivity reactions have been reported with Kogenate FS.
Warn patients of the early signs of hypersensitivity reactions [including hives
(rash with itching), generalized urticaria, tightness of the chest, wheezing,
hypotension] and anaphylaxis. Advise patients to discontinue use of the product
if these symptoms occur and seek immediate emergency treatment with
resuscitative measures such as the administration of epinephrine and oxygen.
• Inhibitor formation may occur at any time in the treatment of a patient with
hemophilia A. Advise patients to contact their physician or treatment center for
further treatment and/or assessment, if they experience a lack of clinical response
to factor VIII replacement therapy, as this may be a manifestation of an inhibitor.
• Advise patients to consult with their healthcare provider prior to travel.
While traveling advise patients to bring an adequate supply of Kogenate FS
based on their current regimen of treatment.
S:10”
8.3 Nursing Mothers
It is not known whether this drug is excreted into human milk. Because many
drugs are excreted into human milk, caution should be exercised if Kogenate FS
is administered to a nursing woman.
15
REFERENCES
1. White GC, Rosendaal F, Aledort LM, Lusher JM, Rothschild C, Ingerslev
J, for the Factor VIII and Factor IX Subcommittee of the Scientific and
Standardization Committee of the International Society on Thrombosis and
Haemostasis. Definitions in hemophilia. Thromb Haemost 85:560-75, 2001.
5. Manco-Johnson MJ, Abshire TC, Shapiro AD, Riske B, Hacker MR, Kilcoyne
R, et al. Prophylaxis versus episodic treatment to prevent joint disease in
boys with severe hemophilia. N Engl J Med 2007;357(6):535-44.
6. Kasper CK: Complications of hemophilia A treatment: factor VIII inhibitors.
Ann NY Acad Sci 614:97-105, 1991.
7. Gouw SC, van den Berg HM, et al: Intensity of factor VIII treatment and
inhibitor development in children with severe hemophilia A: the RODIN
study. Blood 121(20): 4046-4055, 2013.
8. Calvez T, Chambost H, et al: Recombinant factor VIII products and inhibitor
development in previously untreated boys with severe hemophilia A. Blood
124(23): 3398-3408, 2014.
9. Collins PW, Palmer BP, et al: Factor VIII brand and the incidence of factor
VIII inhibitors in previously untreated UK children with severe hemophilia A,
2000-2011. Blood 124(23): 3389-3397, 2014.
10. Franchini M, Coppola A, et al: Systematic Review of the Role of FVIII
Concentrates in Inhibitor Development in Previously Untreated Patients with
Severe Hemophilia A: A 2013 Update. Semin Throm Hemost (39): 752-766, 2013.
11. Vezina C, Carcao M, et al: Incidence and risk factors for inhibitor development
in previously untreated severe haemophilia A patients born between 2005
and 2010. Haemophilia 20(6): 771-776, 2014.
12. Fisher K, Lassila, R, et al. Inhibitor development in haemophilia according
to concentrate: Four-year results from the European HAemophilia Safety
Surveillance (EUHASS) project. Thromb Haemost 113.4, 2015.
13. Barnes C, Lillicrap D, Pazmino-Canizares J, et al: Pharmacokinetics of
recombinant factor VIII (Kogenate-FS®) in children and causes of interpatient pharmacokinetic variability. Haemophilia 12 (Suppl. 4): 40-49, 2006.
Dr. Attal and colleagues also observed a correlation between AHCT and
an increased rate of minimal residual
disease negativity (80% vs. 65%; p<0.001)
and improved time to progression (49%
vs. 35%; p<0.001).
Significantly more patients in the
transplant arm achieved a complete response (59% vs. 49%; P < .01). However,
the high three-year post-randomization
OS rate (88%) remained similar between
study groups.
The researchers recorded 41 second primary malignancies in 39 patients (23 in the AHCT arm and 18 in
the RVD arm). In the transplant arm,
93 percent of patients underwent
AHCT and five toxic deaths occurred
during mobilization or in the actual
transplant phase (1.4%).
A parallel U.S. trial is currently
being conducted that will add to these
results; though the study has a similar
design, patients in both arms are
receiving maintenance lenalidomide
continuously until disease progression.
For now, though, it seems like
AHCT will remain the first choice
for younger patients with previously
untreated MM. “The rate of survival
after three years remains high in both
study arms,” Dr. Attal said during his
presentation of the results. “However,
transplantation is already associated
with a reduced risk for death due to
myeloma. Thus, in the era of new
drugs, transplantation should remain
a standard of care.” ●
T:10.875”
8.2 Labor and Delivery
There is no information available on the effect of factor VIII replacement therapy
on labor and delivery. Kogenate FS should be used only if clinically needed.
stage, standard or high-risk cytogenetics,
and response after the three first cycles of
RVD (complete response or not).
The complete response rate was significantly higher in the transplant arm compared with the RVD arm, the researchers
noted (58% vs. 46%, respectively; p<0.01);
however, three years after randomization, the “extremely high” rate of overall
survival (OS) was similar between the two
study groups (p=0.25), the authors noted.
ASH Social Media
The social media buzz around the ASH
annual meeting continued to grow in
2015. A quick look at the use of the
#ASH15 hashtag shows some remarkable growth over 2014:
TOTAL IMPRESSIONS: 111,432,724
(meaning that more than 100 million
people potentially could have seen the
hashtag on their Twitter timelines —
nearly double last year’s number, when
#ASH14 had 57 million impressions.)
TOTAL TWEETS:
34,409 (and growing)
PARTICIPANTS:
5,515
AVERAGE TWEETS PER HOUR:
179
AVERAGE TWEETS PER PARTICIPANT:
6
January 2016